Autoimmune hepatitis variants: Definitions and treatment
- Michael A Heneghan, MD, MMedSc, FRCPI
Michael A Heneghan, MD, MMedSc, FRCPI
- Consultant Hepatologist & Reader in Hepatology
- Clinical Director for Liver Services
- Institute of Liver Studies, King's College Hospital
Patients with variant forms of autoimmune hepatitis have clinical and serologic findings of autoimmune hepatitis plus features of other forms of chronic liver disease. As will be discussed below, the taxonomy of these variants (often referred to as overlap syndromes) is controversial. The overlap syndromes of autoimmune hepatitis with primary biliary cholangitis and primary sclerosing cholangitis will be reviewed here. The discussion is generally consistent with an international consensus statement published in 2011 .
Autoimmune hepatitis is a chronic hepatitis of unknown etiology characterized by hyperglobulinemia, the presence of circulating autoantibodies, and inflammatory changes on liver histology . Most cases respond to therapy with immunomodulating drugs such as prednisone and azathioprine or 6-mercaptopurine. (See "Autoimmune hepatitis: Disease classification" and "Autoimmune hepatitis: Treatment".)
Patients with certain cholestatic liver diseases (such as primary biliary cholangitis [PBC] and primary sclerosing cholangitis [PSC]) have clinical and serologic features suggesting the presence of autoimmune hepatitis and also may respond to immunosuppressive therapy. Conversely, some patients with features predominantly suggesting autoimmune hepatitis have findings compatible with other forms of chronic liver disease. In a report from the Mayo Clinic, for example, 225 patients with either type I autoimmune hepatitis, PBC, or PSC (162, 37, and 26 patients, respectively) defined by standard criteria, were analyzed for serologic and clinical features suggesting variant forms of autoimmune hepatitis . Among these patients, 18 percent had diseases with overlapping features, including:
●7 percent with autoimmune hepatitis/PBC
●6 percent with autoimmune hepatitis/PSC
- Boberg KM, Chapman RW, Hirschfield GM, et al. Overlap syndromes: the International Autoimmune Hepatitis Group (IAIHG) position statement on a controversial issue. J Hepatol 2011; 54:374.
- Krawitt EL. Autoimmune hepatitis. N Engl J Med 2006; 354:54.
- Czaja AJ. Frequency and nature of the variant syndromes of autoimmune liver disease. Hepatology 1998; 28:360.
- Boberg KM, Fausa O, Haaland T, et al. Features of autoimmune hepatitis in primary sclerosing cholangitis: an evaluation of 114 primary sclerosing cholangitis patients according to a scoring system for the diagnosis of autoimmune hepatitis. Hepatology 1996; 23:1369.
- Ludwig J, Batts KP. Histopathology of autoimmune liver disease. In: Autoimmune Liver Diseases, 2d ed, Krawitt EL, Wiesner RH, Nishioka M (Eds), Elsevier Science Publishers, Amsterdam 1998.
- Czaja AJ. The variant forms of autoimmune hepatitis. Ann Intern Med 1996; 125:588.
- Perrillo RP, Mason AL, Jacob S, Gerber MA. Hepatitis and cholestasis in a middle-aged woman. Hepatology 1996; 24:730.
- Chazouillères O, Wendum D, Serfaty L, et al. Primary biliary cirrhosis-autoimmune hepatitis overlap syndrome: clinical features and response to therapy. Hepatology 1998; 28:296.
- Kuiper EM, Zondervan PE, van Buuren HR. Paris criteria are effective in diagnosis of primary biliary cirrhosis and autoimmune hepatitis overlap syndrome. Clin Gastroenterol Hepatol 2010; 8:530.
- Poupon R, Chazouilleres O, Corpechot C, Chrétien Y. Development of autoimmune hepatitis in patients with typical primary biliary cirrhosis. Hepatology 2006; 44:85.
- Bonder A, Retana A, Winston DM, et al. Prevalence of primary biliary cirrhosis-autoimmune hepatitis overlap syndrome. Clin Gastroenterol Hepatol 2011; 9:609.
- Davis PA, Leung P, Manns M, et al. M4 and M9 antibodies in the overlap syndrome of primary biliary cirrhosis and chronic active hepatitis: epitopes or epiphenomena? Hepatology 1992; 16:1128.
- O'Brien C, Joshi S, Feld JJ, et al. Long-term follow-up of antimitochondrial antibody-positive autoimmune hepatitis. Hepatology 2008; 48:550.
- Ben-Ari Z, Dhillon AP, Sherlock S. Autoimmune cholangiopathy: part of the spectrum of autoimmune chronic active hepatitis. Hepatology 1993; 18:10.
- Colombato LA, Alvarez F, Côté J, Huet PM. Autoimmune cholangiopathy: the result of consecutive primary biliary cirrhosis and autoimmune hepatitis? Gastroenterology 1994; 107:1839.
- Duclos-Vallée JC, Hadengue A, Ganne-Carrié N, et al. Primary biliary cirrhosis-autoimmune hepatitis overlap syndrome. Corticoresistance and effective treatment by cyclosporine A. Dig Dis Sci 1995; 40:1069.
- Goodman ZD, McNally PR, Davis DR, Ishak KG. Autoimmune cholangitis: a variant of primary biliary cirrhosis. Clinicopathologic and serologic correlations in 200 cases. Dig Dis Sci 1995; 40:1232.
- Czaja AJ, Carpenter HA, Santrach PJ, Moore SB. Autoimmune cholangitis within the spectrum of autoimmune liver disease. Hepatology 2000; 31:1231.
- Oertelt S, Rieger R, Selmi C, et al. A sensitive bead assay for antimitochondrial antibodies: Chipping away at AMA-negative primary biliary cirrhosis. Hepatology 2007; 45:659.
- Lohse AW, zum Büschenfelde KH, Franz B, et al. Characterization of the overlap syndrome of primary biliary cirrhosis (PBC) and autoimmune hepatitis: evidence for it being a hepatitic form of PBC in genetically susceptible individuals. Hepatology 1999; 29:1078.
- Joshi S, Cauch-Dudek K, Wanless IR, et al. Primary biliary cirrhosis with additional features of autoimmune hepatitis: response to therapy with ursodeoxycholic acid. Hepatology 2002; 35:409.
- Muratori P, Granito A, Pappas G, et al. The serological profile of the autoimmune hepatitis/primary biliary cirrhosis overlap syndrome. Am J Gastroenterol 2009; 104:1420.
- Romero-Gómez M, Wichmann I, Crespo J, et al. Serum immunological profile in patients with chronic autoimmune cholestasis. Am J Gastroenterol 2004; 99:2150.
- Silveira MG, Talwalkar JA, Angulo P, Lindor KD. Overlap of autoimmune hepatitis and primary biliary cirrhosis: long-term outcomes. Am J Gastroenterol 2007; 102:1244.
- Kaya M, Angulo P, Lindor KD. Overlap of autoimmune hepatitis and primary sclerosing cholangitis: an evaluation of a modified scoring system. J Hepatol 2000; 33:537.
- van Buuren HR, Terkivatan T, Schalm SW, et al. High prevalence of autoimmune hepatitis among patients with primary sclerosing cholangitis. J Hepatol 2000; 33:543.
- Gohlke F, Lohse AW, Dienes HP, et al. Evidence for an overlap syndrome of autoimmune hepatitis and primary sclerosing cholangitis. J Hepatol 1996; 24:699.
- McNair AN, Moloney M, Portmann BC, et al. Autoimmune hepatitis overlapping with primary sclerosing cholangitis in five cases. Am J Gastroenterol 1998; 93:777.
- Gregorio GV, Portmann B, Karani J, et al. Autoimmune hepatitis/sclerosing cholangitis overlap syndrome in childhood: a 16-year prospective study. Hepatology 2001; 33:544.
- Abdalian R, Dhar P, Jhaveri K, et al. Prevalence of sclerosing cholangitis in adults with autoimmune hepatitis: evaluating the role of routine magnetic resonance imaging. Hepatology 2008; 47:949.
- Lewin M, Vilgrain V, Ozenne V, et al. Prevalence of sclerosing cholangitis in adults with autoimmune hepatitis: a prospective magnetic resonance imaging and histological study. Hepatology 2009; 50:528.
- Wilschanski M, Chait P, Wade JA, et al. Primary sclerosing cholangitis in 32 children: clinical, laboratory, and radiographic features, with survival analysis. Hepatology 1995; 22:1415.
- Perdigoto R, Carpenter HA, Czaja AJ. Frequency and significance of chronic ulcerative colitis in severe corticosteroid-treated autoimmune hepatitis. J Hepatol 1992; 14:325.
- Abdo AA, Bain VG, Kichian K, Lee SS. Evolution of autoimmune hepatitis to primary sclerosing cholangitis: A sequential syndrome. Hepatology 2002; 36:1393.
- Floreani A, Rizzotto ER, Ferrara F, et al. Clinical course and outcome of autoimmune hepatitis/primary sclerosing cholangitis overlap syndrome. Am J Gastroenterol 2005; 100:1516.
- Chazouillères O, Wendum D, Serfaty L, et al. Long term outcome and response to therapy of primary biliary cirrhosis-autoimmune hepatitis overlap syndrome. J Hepatol 2006; 44:400.
- Al-Chalabi T, Portmann BC, Bernal W, et al. Autoimmune hepatitis overlap syndromes: an evaluation of treatment response, long-term outcome and survival. Aliment Pharmacol Ther 2008; 28:209.
- Aw MM, Dhawan A, Samyn M, et al. Mycophenolate mofetil as rescue treatment for autoimmune liver disease in children: a 5-year follow-up. J Hepatol 2009; 51:156.
- SCORING SYSTEMS
- AUTOIMMUNE HEPATITIS-PBC OVERLAPS
- AUTOIMMUNE HEPATITIS-PSC OVERLAPS
- AMA-positive without histologic evidence of PBC
- ANA and/or SMA-positive with histologic changes suggesting PBC
- Autoimmune hepatitis-PSC overlap
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS